The invention relates to a biocompatible injectable filler composition, such as a dermal filler (e.g., superficial dermal filler, mid-dermal filler or deep dermal filler) or subdermal filler composition, methods for their preparation, and a method of its use in aesthetic medical applications such as tissue augmentation and restoration.
Aesthetic medicine involves the treatment of patients who desire to modify their appearance or desire to reverse aesthetic problems caused by aging, accidents, or malformation. The majority of aesthetic medical treatments involve minimally invasive procedures, such as dermal and subdermal filler injections. A dermal filler is a product that is injected or placed into the dermis. Subdermal fillers are those that are placed underneath the dermis in the subcutis. Desirably the dermal or subdermal filler when injected in the skin or tissue adds bulk to the area of injection restoring or increasing soft-tissue volume. Restoration of facial volume using fillers can rebalance facial proportions, increase symmetry, and reduce wrinkles and volume loss, particularly in the lower two thirds of the face (e.g., the nasolabial fold area). Dermal and subdermal filler injections can produce immediate results, but usually with limited duration of action.
Fillers can be classified based on their source (e.g., autologous, biological, or synthetic), based on duration of action (in number of months), and based on degree of reversibility (e.g., rapidly reversible, slowly biodegradable but not reversible, and nonbiodegradeable).
Desirably, dermal fillers are biocompatible, nonantigenic, nontoxic, noncarcinogenic and nonteratogenic. In addition, dermal fillers desirably produce consistent and reproducible outcomes with minimal migration from the injection site, maximal safety, minimal adverse effects (e.g., pain or stinging during injection, acute inflammation, infection, bruising, swelling, tenderness, skin discoloration delayed (>24 hrs) hypersensitivity or inflammation), retention of softness or flexibility in the tissue after injection, and ease of administration. Furthermore it is desirable to use a filler composition that is not permanent, yet provides adequate duration of effect, on the order of 12 months or more, so as to minimize the need for retreatment and the associated costs, along with good filler persistence (e.g., without development of nodules, hard lumps, or tenderness). While dermal fillers are known that provide some of these desirable properties, no single filler possesses all of these characteristics.
U.S. Pat. No. 7,968,110, entitled “Tissue augmentation material and method,” teaches a tissue augmentation material comprising smooth rounded, substantially spherical particle of hydroxyapatite having a particle size large enough to avoid phagocytosis (i.e., larger than 15 microns) with a preferred particle size range of 30 to 150 microns to facilitate injection. The inventors teach spray drying a slurry of 20 to 40% hydroxyapatite to produce the hydroxyapatite particles having a particle size distribution between 38 to 63 microns that are of very high density (e.g., about 95% to 100%).
The present invention relates to a biocompatible filler composition (e.g., a dermal or subdermal filler composition) comprising porous calcium phosphate particles having a small particle size in combination with a thermoreversible gelling agent that is nontoxic, provides improved flexibility, and a long duration of effect.